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1.
J Endocrinol Invest ; 46(7): 1305-1316, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36802028

ABSTRACT

PURPOSE: Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves' disease. First-line treatment for DON consists of high-dose intravenous methylprednisolone (ivMP), followed by immediate orbital decompression (OD) if the response is poor or absent as recommended by the 2021 European Group on Graves' orbitopathy guidelines. The safety and efficacy of the proposed therapy have been proven. However, consensus regarding possible therapeutic options for patients with contraindications to ivMP/OD or resistant form of disease is missing. This paper aims to provide and summarize all available data regarding possible alternative treatment strategies for DON. METHODS: A comprehensive literature search within an electronic database was performed including data published until December 2022. RESULTS: Overall, 52 articles describing use of emerging therapeutic strategies for DON were identified. Collected evidence indicates that biologics, including teprotumumab and tocilizumab, may be considered as an important possible treatment option for DON patients. Rituximab should be avoided in DON due to conflicting data and risk of adverse events. Orbital radiotherapy could be beneficial for patients with restricted ocular motility classified as poor surgical candidates. CONCLUSION: Only a limited number of studies have been dedicated to the therapy of DON, mostly retrospective with a small sample size. Clear criteria regarding diagnosis and resolution of DON do not exist, which restricts comparison of therapeutic outcomes. Randomized clinical trials and comparison studies with long-term follow-ups are necessary to verify the safety and efficacy of each therapeutic option for DON.


Subject(s)
Graves Disease , Graves Ophthalmopathy , Optic Nerve Diseases , Humans , Graves Ophthalmopathy/diagnosis , Optic Nerve Diseases/diagnosis , Retrospective Studies , Methylprednisolone , Glucocorticoids , Graves Disease/drug therapy
2.
Mol Genet Metab ; 131(1-2): 23-37, 2020.
Article in English | MEDLINE | ID: mdl-33093005

ABSTRACT

The nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD) is the fourth in a series of web-based guidelines focusing on the diet treatment for inherited metabolic disorders and follows previous publication of guidelines for maple syrup urine disease (2014), phenylketonuria (2016) and propionic acidemia (2019). The purpose of this guideline is to establish harmonization in the treatment and monitoring of individuals with VLCAD of all ages in order to improve clinical outcomes. Six research questions were identified to support guideline development on: nutrition recommendations for the healthy individual, illness management, supplementation, monitoring, physical activity and management during pregnancy. This report describes the methodology used in its development including review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; expert input through two Delphi surveys and a nominal group process; and external review from metabolic physicians and dietitians. It includes the summary statements of the nutrition management recommendations for each research question, followed by a standardized rating based on the strength of the evidence. Online, open access of the full published guideline allows utilization by health care providers, researchers and collaborators who advise, advocate and care for individuals with VLCAD and their families and can be accessed from the Genetic Metabolic Dietitians International (https://GMDI.org) and Southeast Regional Genetics Network (https://southeastgenetics.org/ngp) websites.


Subject(s)
Acyl-CoA Dehydrogenase, Long-Chain/genetics , Congenital Bone Marrow Failure Syndromes/diet therapy , Lipid Metabolism, Inborn Errors/diet therapy , Mitochondrial Diseases/diet therapy , Muscular Diseases/diet therapy , Nutrition Policy , Acyl-CoA Dehydrogenase, Long-Chain/metabolism , Congenital Bone Marrow Failure Syndromes/genetics , Congenital Bone Marrow Failure Syndromes/metabolism , Congenital Bone Marrow Failure Syndromes/pathology , Female , Guidelines as Topic , Humans , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/metabolism , Lipid Metabolism, Inborn Errors/pathology , Mitochondrial Diseases/genetics , Mitochondrial Diseases/metabolism , Mitochondrial Diseases/pathology , Muscular Diseases/genetics , Muscular Diseases/metabolism , Muscular Diseases/pathology , Nutrition Therapy , Pregnancy
4.
Nanoscale ; 11(28): 13458-13468, 2019 Jul 18.
Article in English | MEDLINE | ID: mdl-31287475

ABSTRACT

The large number of nanomaterial-based applications emerging in the materials and life sciences and the foreseeable increasing use of these materials require methods that evaluate and characterize the toxic potential of these nanomaterials to keep safety risks to people and environment as low as possible. As nanomaterial toxicity is influenced by a variety of parameters like size, shape, chemical composition, and surface chemistry, high throughput screening (HTS) platforms are recommended for assessing cytotoxicity. Such platforms are not yet available for genotoxicity testing. Here, we present first results obtained for application-relevant nanomaterials using an automatable genotoxicity platform that relies on the quantification of the phosphorylated histone H2AX (γ-H2AX) for detecting DNA double strand breaks (DSBs) and the automated microscope system AKLIDES® for measuring integral fluorescence intensities at different excitation wavelengths. This platform is used to test the genotoxic potential of 30 nm-sized citrate-stabilized gold nanoparticles (Au-NPs) as well as micellar encapsulated iron oxide nanoparticles (FeOx-NPs) and different cadmium (Cd)-based semiconductor quantum dots (QDs), thereby also searching for positive and negative controls as reference materials. In addition, the influence of the QD shell composition on the genotoxic potential of these Cd-based QDs was studied, using CdSe cores as well as CdSe/CdS core/shell and CdSe/CdS/ZnS core/shell/shell QDs. Our results clearly revealed the genotoxicity of the Au-NPs and its absence in the FeOx-NPs. The genotoxicity of the Cd-QDs correlates with the shielding of their Cd-containing core, with the core/shell/shell architecture preventing genotoxicity risks. The fact that none of these nanomaterials showed cytotoxicity at the chosen particle concentrations in a conventional cell viability assay underlines the importance of genotoxicity studies to assess the hazardous potential of nanomaterials.


Subject(s)
Cadmium/chemistry , Histones/metabolism , Mutagenicity Tests/methods , Nanostructures/toxicity , Quantum Dots/chemistry , Cadmium/toxicity , Cell Survival , DNA Breaks, Double-Stranded/drug effects , Ferric Compounds/chemistry , Ferric Compounds/toxicity , Fluorometry , Gold/chemistry , Gold/toxicity , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mutagenicity Tests/instrumentation , Nanostructures/chemistry , Particle Size , Phosphorylation/drug effects , Quantum Dots/toxicity
5.
Neoplasma ; 65(3): 449-454, 2018 Mar 14.
Article in English | MEDLINE | ID: mdl-29788732

ABSTRACT

The main objective of the ACOSOG Z0011 trial was to determine the impact of abandoning complete axillary lymph node dissection (ALND) on survival of breast cancer patients with sentinel node lymph (SLN) metastasis in whom breast conserving therapy (BCT) had been performed. The aim of our study was to assess the clinical value of intra-operative histopathological examination of SLN. Our study comprised 1284 invasive breast cancer patients in whom sentinel lymph node biopsy (SLNB) was carried out. SLN intra-operative histopathological assessment was routinely performed in patients treated within the first period (07.2013-06.2014). However, the decision regarding intra-operative assessment was made by the surgeon for the patients who underwent this evaluation in the later period 07.2014-06.2015 and were submitted for BCT. BCT was performed in 72.4% of patients. In total, 316 patients (24.6%) developed SLN-metastasis. Within the period 07.2014-06.2015, SLN intra-operative microscopic evaluation was performed in 20.8% of patients submitted for BCT. ALND was omitted in 27.5% of patients demonstrating SLN metastasis, in comparison with 15.5% of the group from the previous period (p=0.0094). The proportion of patients demonstrating macrometastasis in SLN who received conservative treatment to the axilla increased from 5.4% to 23.1% (p=0.0007). The choice of SLN final histopathological assessment may allow for deferral of decision on more extensive surgery of the axilla in patients submitted for SLNB. The omission of routinely-performed SLN intra-operative histopathological evaluation has led to a statistically significant increase in the proportion of patients in whom complete ALND was avoided.


Subject(s)
Breast Neoplasms/diagnosis , Sentinel Lymph Node Biopsy , Sentinel Lymph Node/pathology , Axilla , Breast Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Mastectomy, Segmental
6.
Mol Genet Metab ; 124(1): 57-63, 2018 05.
Article in English | MEDLINE | ID: mdl-29526615

ABSTRACT

Ethylmalonic encephalopathy (EE) is a devastating neurodegenerative disease caused by mutations in the ETHE1 gene critical for hydrogen sulfide (H2S) detoxification. Patients present in infancy with hypotonia, developmental delay, diarrhea, orthostatic acrocyanosis and petechiae. Biochemical findings include elevated C4, C5 acylcarnitines and lactic and ethylmalonic acid (EMA) in body fluids. Current treatment modalities include metronidazole and N-acetylcysteine (NAC) to lower the production and promote detoxification of toxic H2S. Patients are typically identified after the onset of clinical symptoms and there is limited information about long term response to treatment. We report the findings of two unrelated patients with EE, identified through newborn screening, who were managed with conventional treatment (NAC, metronidazole alternated with neomycin) and in patient 2, a novel dietary treatment restricting sulfur containing amino acids. Pathogenic mutations were confirmed in the ETHE1 gene (homozygous splice site mutation in patient 1, c.505 + 1G > A; compound heterozygous mutations in patient 2, c.131_132delAG + c.566delG). Both patients were started on metronidazole and NAC by 10 weeks of age and treated for 23 months. Patient 1 did not accept the metabolic formula due to palatability and parental refusal for gastrostomy tube placement. She demonstrated improved biomarkers (EMA, lactic acid and thiosulfate) and an attenuated clinical course. Patient 2 was started on a low methionine and cysteine diet at 8 months of age utilizing SOD Anamix® Early Years, (Nutricia). Baseline EMA levels were (642 mg/g Cr; n = 2) and decreased with medical treatment by 38% to a mean of 399 (n = 4, SD = 71, p 0.0013). With dietary treatment EMA levels were further reduced by 42% to a mean of 233 (n = 8, SD = 52, p 0.0030). Lactic acid, thiosulfates and clinical outcomes were also improved. Our long-term follow-up confirms previous reports of clinical improvement with NAC and metronidazole treatment. Additionally, our studies suggest that a diet restricted in sulfur-containing amino acids results in further improvement in clinical outcomes and biochemical markers.


Subject(s)
Amino Acids/administration & dosage , Brain Diseases, Metabolic, Inborn/diet therapy , Brain Diseases, Metabolic, Inborn/drug therapy , Neonatal Screening , Purpura/diet therapy , Purpura/drug therapy , Acetylcysteine/therapeutic use , Amino Acids/chemistry , Biomarkers , Brain Diseases, Metabolic, Inborn/diagnosis , Cysteine , Diet/methods , Female , Humans , Infant , Infant, Newborn , Lactic Acid/analysis , Male , Malonates/analysis , Methionine , Metronidazole/therapeutic use , Mitochondrial Proteins/genetics , Mutation , Nucleocytoplasmic Transport Proteins/genetics , Purpura/diagnosis , Sulfur
7.
J Physiol Pharmacol ; 67(2): 235-42, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27226183

ABSTRACT

UNLABELLED: Multiple sclerosis (MS) prevalence is higher in geographic regions with less sunlight exposure. Melatonin participates in the effects of sunlight in healthy individuals and could play a role in MS pathophysiology. Melatonin crosses the blood-brain barrier and exerts antioxidative, immunomodulatory, and anti-inflammatory effects. Chronic fatigue syndrome concerns 80 - 90% MS patients. The pathophysiology of chronic fatigue syndrome is unknown, however activation of immune, inflammatory, oxidative and nitrosative stress mechanisms and plasma lipid peroxide elevation was reported. Homocysteine increases plasma lipid hydroperoxides levels. The aim was to determine the effect of melatonin supplementation on chronic fatigue syndrome in MS patients and evaluate plasma lipid hydroxyperoxides (LHP) and homocysteine concentrations as a potential biochemical fatigue biomarkers. Into a case-control prospective study 102 MS patients divided according receiving immunomodifying MS treatment into groups: RRMS-pretreated, RRMS-INF-beta, SP/PPMS-mitoxantrone, RRMS-relapse were enrolled. Patients were supplemented with melatonin over 90 days. Plasma LHP, homocysteine concentration, brain MRI and fatigue score were examined. Results show that LHP concentrations were significantly higher in all studied MS groups vs. CONTROLS: In all MS patient groups melatonin application resulted in significant decrease in plasma LHP concentrations. Plasma homocysteine concentration was similar in healthy people, RRMS-pretreated, RRMS-INF-beta and SP/PP-MS-mitoxantrone groups. However, in the RRMS-relapse group plasma levels of homocysteine were significantly higher compared to the RRMS-pretreated group. There were no significant differences in plasma homocysteine concentration in the studied groups before and after melatonin application. The fatigue score was significantly lower in RRMS pretreated group compared to RRMS-INF-beta and SP/PP MS-mitoxantrone treated patients. Plasma lipid hydroxyperoxides could be potential biochemical chronic fatigue syndrome biomarker in MS patients and homocysteine could be a potential marker of acute phase of MS. Melatonin exerts beneficial effects in MS patients based on its' proved antioxidative properties.


Subject(s)
Antioxidants/pharmacology , Dietary Supplements , Fatigue Syndrome, Chronic/blood , Homocysteine/blood , Lipid Peroxides/blood , Melatonin/pharmacology , Multiple Sclerosis/blood , Adult , Antioxidants/therapeutic use , Brain/diagnostic imaging , Fatigue Syndrome, Chronic/drug therapy , Female , Humans , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Interferon-beta/pharmacology , Interferon-beta/therapeutic use , Magnetic Resonance Imaging , Male , Melatonin/therapeutic use , Middle Aged , Mitoxantrone/pharmacology , Mitoxantrone/therapeutic use , Multiple Sclerosis/drug therapy , Young Adult
8.
J Endocrinol Invest ; 38(6): 635-42, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25596662

ABSTRACT

INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate the concentration of 25-hydroxycholecalciferol and parameters of calcium-phosphate metabolism at different periods of relapsing-remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: Forty-five patients, residents of Poland (49°-50°, N), were enrolled in the study, i.e. 15 immediately after the diagnosis of RRMS, 15 at the early stage and 15 at the advanced stage of RRMS. The results were compared to values obtained in 20 age- and sex-matched controls. RESULTS: Lower serum concentrations of 25-hydroxycholecalciferol and ionised calcium were found in patients compared to the control group. In patients with the disease duration of 5-6 years, concentrations of 25-hydroxycholecalciferol and ionised calcium were lower than in patients in the earlier period of RRMS. The inverse and clearer direction of changes was found in parathormone serum concentration in patients compared to the controls. In patients with a longer disease duration, a significantly lower 25-hydroxycholecalciferol concentration was found in female patients compared to male patients. In patients, more frequent 25-hydroxycholecalciferol and unsaturated fatty acids' supplementation was observed compared to the controls. CONCLUSIONS: In RRMS patients, calcium-phosphate metabolism is disturbed which increases during disease progression.


Subject(s)
Calcifediol/blood , Calcium/blood , Multiple Sclerosis, Relapsing-Remitting/blood , Parathyroid Hormone/blood , Phosphorus/blood , Adult , Alkaline Phosphatase/blood , Female , Humans , Male , Middle Aged , Vitamin D/analogs & derivatives , Vitamin D/blood , Young Adult
9.
J Periodontal Res ; 50(5): 594-601, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25369875

ABSTRACT

BACKGROUND AND OBJECTIVE: The influence of diabetes mellitus (DM) on the hemodynamics of periodontal tissues has not been assessed previously. The primary objective of this study was to validate optical spectroscopy as a periodontal diagnostic tool for subjects with type 2 DM and chronic periodontitis. MATERIAL AND METHODS: Using a portable optical near-infrared spectrometer, optical spectra were obtained from healthy (n = 127), gingivitis (n = 115), and periodontitis (n = 109) sites of 65 subjects with type 2 DM and chronic periodontitis. Healthy (n = 65) sites of 15 nondiabetic subjects without periodontitis were used as controls. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering-loss function was used to determine the relative contribution of deoxygenated hemoglobin and oxygenated hemoglobin (HbO2 ) to the overall spectrum. The balance between tissue oxygen delivery and oxygen utilization in periodontal tissues was assessed. RESULTS: In diabetic subjects, tissue oxygen saturation and HbO2 concentration were significantly decreased in the periodontitis sites (p < 0.01) compared with the healthy and gingivitis sites. Furthermore, tissue oxygenation in healthy sites of control subjects was significantly higher than that in sites of diabetic subjects (p < 0.01). CONCLUSION: In summary, the results of this study suggest that optical spectroscopy can monitor the hemodynamic profile in diabetic subjects with chronic periodontitis. Furthermore, healthy sites of diabetic subjects presented lower tissue oxygenation than did those of nondiabetic subjects.


Subject(s)
Periodontium , Gingivitis/diagnosis , Hemodynamics , Humans , Periodontitis , Spectrum Analysis
10.
Gesundheitswesen ; 77 Suppl 1: S60-1, 2015 Sep.
Article in German | MEDLINE | ID: mdl-23549654

ABSTRACT

The aim of this study was to assess the effects of 2 German school-based primary prevention programmes for (pre)adolescents, aged 11-13 years, with 9 manual-guided lessons. 92 (PriMa, n=1,553 girls) and 22 (Torera, n=256 boys, 277 girls) Thuringian secondary schools participated in controlled trials with pre-post assessment. Girls and students at risk showed significant improvements of conspicuous eating behaviour and body self-esteem with small to medium effect sizes. Implementation costs were € 2.50 per student.


Subject(s)
Adolescent Health/statistics & numerical data , Feeding and Eating Disorders/epidemiology , Feeding and Eating Disorders/prevention & control , Peer Influence , Risk Reduction Behavior , School Health Services/statistics & numerical data , Adolescent , Child , Diet, Healthy , Feeding and Eating Disorders/psychology , Female , Germany/epidemiology , Humans , Male , Prevalence , Program Evaluation , Psychology, Adolescent , Risk Factors , Socioeconomic Factors , Students , Treatment Outcome
11.
J Physiol Pharmacol ; 65(5): 659-71, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25371525

ABSTRACT

The aim of this study was to determine the effectory mechanisms: vasopressin, renin-angiotensin system and proopiomelanocortin-derived peptides (POMC), partaking in the effects of serotonin through central serotonin 1A receptor (5-HT1A) receptors in haemorrhagic shock in rats. The study was conducted on male Wistar rats. All experimental procedures were carried out under full anaesthesia. The principal experiment included a 2 hour observation period in haemorrhagic shock. Drugs used - a selective 5-HT1A agonist 8-OH-DPAT (5 µg/5 µl); V1a receptor antagonist [ß-mercapto-ß, ß-cyclo-pentamethylenepropionyl(1),O-me-Tyr(2),Arg(8)]AVP (10 µg/kg); angiotensin type I receptor antagonist (AT1) ZD7155 (0.5 mg/kg, i.v.); angiotensin-converting-enzyme inhibitor captopril (30 mg/kg, i.v.); melanocortin type 4 (MC4) receptor antagonist HS014 (5 µg, i.c.v.). There was no influence of ZD715, captopril or blocking of the V1a receptors on changes in the heart rate (HR), mean arterial pressure (MAP), peripheral blood flow or resistance caused by the central stimulation of 5-HT1A receptors (P≥0.05). However, selective blocking of central MC4 receptors caused a slight, but significant decrease in HR and MAP (P<0.05). POMC derivatives acting via the central MC4 receptor participate in the resuscitative effects of 8-OH-DPAT. The angiotensin and vasopressin systems do not participate in these actions.


Subject(s)
8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Pro-Opiomelanocortin/physiology , Receptor, Melanocortin, Type 4/physiology , Serotonin 5-HT1 Receptor Agonists/pharmacology , Shock, Hemorrhagic/physiopathology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Arterial Pressure/drug effects , Captopril/pharmacology , Heart Rate/drug effects , Male , Naphthyridines/pharmacology , Peptides, Cyclic/pharmacology , Rats , Rats, Wistar , Receptor, Melanocortin, Type 4/antagonists & inhibitors , Receptors, Vasopressin/physiology
12.
J Physiol Pharmacol ; 65(4): 543-50, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25179086

ABSTRACT

The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Several studies have reported that the quality of life is worse in patients with MS than in healthy controls, with a higher prevalence of sleep disturbances, depression and fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity and its' influence on impact of the quality of life of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The EDSS, MRI examinations and Multiple Sclerosis Impact Scale (MSIS-29) questionnaire was completed. Marked increase in serum MDA concentration in all MS patients groups was observed and after melatonin treatment decreased significantly in interferons-beta and glatiramer acetate-treated groups, but not in mitoxantrone-treated group. A significant increase in SOD activity compared to controls only in glatiramer acetate-treated group was observed. After 3 months melatonin supplementation the SOD activity increased compared to initial values in interferons beta-treated groups. A significant increase in both MSIS-29-PHYS and MSIS-29-PSYCH items mean scores only in the MX group as compared to other groups was observed. There were no significant differences in mean MSIS-29-PHYS was observed before and after melatonin therapy. Melatonin supplementation caused a decrease in mean MSIS-29-PSYCH scores compared to initial values in interferons beta-treated groups. Finding from our study suggest that melatonin can act as an antioxidant and improves reduced quality in MS patients.


Subject(s)
Antioxidants/pharmacology , Malondialdehyde/blood , Melatonin/pharmacology , Multiple Sclerosis/blood , Multiple Sclerosis/psychology , Superoxide Dismutase/blood , Adjuvants, Immunologic/therapeutic use , Adult , Dietary Supplements , Female , Glatiramer Acetate , Humans , Immunosuppressive Agents/therapeutic use , Interferon beta-1a , Interferon beta-1b , Interferon-beta/therapeutic use , Male , Middle Aged , Mitoxantrone/therapeutic use , Multiple Sclerosis/drug therapy , Neuropsychological Tests , Peptides/therapeutic use , Quality of Life , Severity of Illness Index , Young Adult
13.
J Physiol Pharmacol ; 65(1): 135-43, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24622838

ABSTRACT

The discovery of MT1, MT2, and MT3 melatonin receptors on adipose tissue cells gives grounds for considering the possibility of melatonin as a factor which influences energy storage through modulation of metabolism and adipocyte proliferation. To date only a few contradictory studies have been published on the influence of melatonin on preadipocytes. The aim of the present study is to evaluate the influence of melatonin at physiological and supraphysiological concentrations on the proliferation of 3T3-L1 murine preadipocytes after 3 and 24 hours of the experiment and to determine the participation of membrane melatonin MT2 receptors, and for the first time--MT3, in its melatonin action during a 24-hour experiment. The 3T3-L1 murine preadipocyte cell line were cultured with or without melatonin at 10⁻³ and 10⁻9 mol/L, with or without melatonin antagonists luzindole (10⁻4 mol/L) and prazosin (10⁻5 mol/L). Cell proliferation was determined by means of labeled [³H]-thymidine incorporation in the DNA of the cell. Melatonin at both physiological and supraphysiological concentrations has a stimulating effect on the number of 3T3-L1 preadipocytes. The application of luzindole inhibits the above effect of melatonin both at 10⁻³ mol/L and 10⁻9 mol/L concentrations (P<0.05). The presence of prazosin does not have a statistically significant influence on the effects of melatonin action. Summarizing, it has been proven that melatonin exerts a proproliferative effect on 3T3-L1 preadipocytes at physiological and supraphysiological concentrations, partially by MT2, and not by MT3 receptors.


Subject(s)
Adipocytes/drug effects , DNA/metabolism , Melatonin/pharmacology , Receptor, Melatonin, MT2/metabolism , Thymidine/metabolism , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Animals , Cell Proliferation/drug effects , Mice , Prazosin/pharmacology , Receptor, Melatonin, MT2/antagonists & inhibitors , Receptors, Melatonin/antagonists & inhibitors , Receptors, Melatonin/metabolism , Tryptamines/pharmacology
14.
Prev Sci ; 15(4): 557-69, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23609793

ABSTRACT

Representative surveys indicate that eating disorders are an increasing problem, especially among (pre)adolescents. We assessed the effects of a German school-based primary prevention program ("Torera") for seventh graders. Torera especially relates to pathological eating behavior in the realm of bulimia nervosa or binge eating disorder. The program is built upon two previously evaluated modules for sixth graders with a gender-specific adaption. The coeducational intervention involves nine manual-guided lessons touching a wide range of eating-related problems. Twenty-two Thuringian secondary schools (n = 256 boys and 277 girls, aged 11-13 years at baseline) participated in a trial with 2 control groups (untreated and pretreated) with pre-post assessment. Primary outcomes were conspicuous eating behavior and body self-esteem, measured by standardized questionnaires (SCOFF, EAT-26D, and FBeK). Girls and students at risk showed significant improvement with small (d = 0.35) to medium (d = 0.66) effect sizes on eating behavior, significantly mediated by body self-esteem. Boys only improved with respect to eating attitudes, revealing a small effect size (d = 0.35). With relatively low implementation costs (about 2.50 per student), Torera provides an efficient model for reducing risky eating behavior and strengthening body self-esteem without negative side effects. To improve the effectiveness of the intervention, further research efforts focusing on at-risk groups (secondary prevention) and structural actions for prevention (e.g., offering healthy school catering) are needed.


Subject(s)
Feeding and Eating Disorders/prevention & control , Risk Reduction Behavior , Adolescent , Attitude to Health , Child , Feeding and Eating Disorders/psychology , Female , Germany , Humans , Male
15.
J Physiol Pharmacol ; 64(2): 219-29, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23756397

ABSTRACT

The bleeding and haemorrhage is strictly related with accidents and many medical procedures. In some conditions it leads to hypovolaemia and further to hypovolaemic shock. Under conditions of haemorrhagic shock, heart rate and blood pressure critically collapse. Reversing the sympathoinhibitory phase of hypovolaemia could be crucial for clinical management of injured patients after haemorrhage. Systemic administration of 5-HT1A agonists seams to produce resuscitating effects. The aim of this study was to investigate the participation of central serotonin and, in particular, 5-HT1A receptors in cardiovascular regulation in haemorrhagic shock in rats. Intracerebroventricular (i.c.v.) administration of serotonin (5-HT) increased the heart rate (HR), mean arterial pressure (MAP) and implicated that all haemorrhaged animals survived for the whole observation time (2 hours). Similar, although significantly more minor, effects were achieved after selective 5-HT1A activation. Moreover, the i.c.v. administration of selective 5-HT1A antagonist before i.c.v. 5-HT injection partially inhibited 5-HT induced changes. The results of the present work indicate that 5-HT plays an important role in the reversal of the haemorrhagic shock in rats. These effects are at least partially dependent on activation of 5-HT1A receptors.


Subject(s)
Receptor, Serotonin, 5-HT1A/physiology , Serotonin/pharmacology , Shock, Hemorrhagic/physiopathology , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Male , Piperazines/pharmacology , Rats , Rats, Wistar , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology
16.
J Physiol Pharmacol ; 63(6): 683-90, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23388485

ABSTRACT

Mitoxantrone (MX) is approved for the treatment of aggressive relapsing-remitting, secondary-progressive and progressive-relapsing form of multiple sclerosis (MS). The mechanism of its action is multiaxial, however, it is not free from side effects. The causes of the side effects are still unknown and require further investigation. The aim of this study was to investigate the influence of MX therapy on enzymatic parameters of endogenous antioxidative status: manganese and copper/zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase (CAT), glutathione peroxidase (GSH-Px) and lipid peroxidation marker--malondialdehyde (MDA) in blood serum and cerebrospinal fluid (CSF) in patients suffering from MS. After the MX therapy serum and the CSF MDA concentrations increased significantly. We reported that MnSOD activities decrease in serum and the CSF, while, surprisingly, the serum Cu/ZnSOD activity increases after the MX therapy. We also noted a marked decrease in CSF CAT and GSH-Px activity after the MX treatment. Our results strongly suggest the influence of MX therapy on oxidation/antioxidation status of serum and the CSF. These findings open up new opportunities for a better understanding of underlying physiopathological events in MS and provide a new insight into MX's mechanisms of action, especially its potent side effects.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Enzymes/blood , Enzymes/cerebrospinal fluid , Malondialdehyde/blood , Malondialdehyde/cerebrospinal fluid , Mitoxantrone/therapeutic use , Multiple Sclerosis/drug therapy , Oxidative Stress/drug effects , Analysis of Variance , Anti-Inflammatory Agents/adverse effects , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Catalase/blood , Catalase/cerebrospinal fluid , Glutathione Peroxidase/blood , Glutathione Peroxidase/cerebrospinal fluid , Humans , Lipid Peroxidation/drug effects , Mitoxantrone/adverse effects , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/enzymology , Superoxide Dismutase/blood , Superoxide Dismutase/cerebrospinal fluid , Time Factors , Treatment Outcome
17.
Article in German | MEDLINE | ID: mdl-21626381

ABSTRACT

The decision to measure or to ask about data concerning height and weight in order to calculate body mass index (BMI) has an influence on the economy and validity of the measurements. Although self-reported information is less expensive, this information may possibly have a bias on the determined prevalences of different weight groups. Using representative data from the KiGGS study with a comparison of directly measured and self-reported BMI data, Kurth and Ellert (2010) developed two correction formulas for prevalences resulting from self-reported information. The aim of the study was to examine the practicability of the proposed correction formulas on our own data concerning self-reported BMI data of 11- to 13-year-old girls (n=1,271) and to assess the plausibility of the corrected measurements. As a result, the prevalences of our own data changed in the expected direction both for underweight and for overweight. Both formulas were found to be practicable, the consideration of the subjective weight status (formula 2) resulted in a greater change in prevalences compared to the first correction formula.


Subject(s)
Algorithms , Body Mass Index , Diagnostic Self Evaluation , Models, Biological , Adolescent , Child , Computer Simulation , Female , Humans , Reproducibility of Results , Sensitivity and Specificity
18.
J Periodontal Res ; 46(3): 382-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21392007

ABSTRACT

BACKGROUND AND OBJECTIVE: Optical spectroscopy has been proposed to measure regional tissue hemodynamics in periodontal tissue. The objective of this study was to further evaluate the diagnostic potential of optical spectroscopy in peri-implant inflammation in vivo by assessing multiple inflammatory parameters (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) simultaneously. MATERIAL AND METHODS: A cross-sectional study was performed in a total of 64 individuals who presented with dental implants in different stages of inflammation. In brief, visible-near-infrared spectra were obtained, processed and evaluated from healthy (n = 151), mucositis (n = 70) and peri-implantitis sites (n = 75) using a portable spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was employed to determine the relative contribution of each inflammatory component to the overall spectrum. RESULTS: Tissue oxygenation at peri-implantitis sites was significantly decreased (p < 0.05) when compared with that at healthy sites, which was largely due to an increase in deoxyhemoglobin and a decrease in oxyhemoglobin at the peri-implantitis sites compared with the mucositis and healthy sites. In addition, the tissue hydration index derived from the optical spectra in mucositis was significantly higher than that in other groups (p < 0.05). CONCLUSION: In summary, the results of this study revealed that hemodynamic alterations can be detected around diseased peri-implant sites by optical spectroscopy, and this method may be considered an alternative and feasible approach for the monitoring and diagnosis of peri-implant diseases.


Subject(s)
Peri-Implantitis/diagnosis , Spectrum Analysis/methods , Adult , Aged , Aged, 80 and over , Algorithms , Alveolar Bone Loss/classification , Cross-Sectional Studies , Dental Plaque Index , Edema/diagnosis , Feasibility Studies , Female , Gingival Hemorrhage/classification , Hemoglobins/analysis , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Optical Fibers , Oxygen/blood , Oxygen Consumption/physiology , Oxyhemoglobins/analysis , Peri-Implantitis/pathology , Periodontal Pocket/classification , Periodontium/anatomy & histology , Radiography, Dental, Digital , Spectrophotometry, Infrared , Spectrum Analysis/instrumentation , Stomatitis/diagnosis
19.
Article in German | MEDLINE | ID: mdl-21347768

ABSTRACT

The onset of puberty is considered a critical period for the development of overweight and obesity. For prevention purposes, we developed the school-based intervention program TOPP (Teenage Obesity Prevention Program), especially for boys. In order to test the effectiveness, we conducted a controlled study using a pre-post design. A total of 84 schools in Thuringian, Germany, with 1,199 boys participated in the study. Program effectiveness was analyzed with mostly standardized questionnaires referring to body-related self esteem, eating behavior, physical activity, teasing, and knowledge. The program was performed during the course of a school project within at least 3 weeks or during the regular school lessons for more than 6 weeks. After 9×90-minute, manual-based lessons, including interactive exercises and poster-based group discussions, significant improvement was only reached for nutritional knowledge. As a main outcome, it could be demonstrated how an area-wide prevention program with low costs could be successfully implemented. The school environment enables us to create a universal, socially equitable, and low-threshold access.


Subject(s)
Health Promotion/statistics & numerical data , Obesity/epidemiology , Obesity/prevention & control , Primary Prevention/statistics & numerical data , Program Evaluation , Adolescent , Germany/epidemiology , Humans , Male , Prevalence , Risk Assessment , Risk Factors , Treatment Outcome , Young Adult
20.
Radiat Prot Dosimetry ; 143(2-4): 311-4, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21216730

ABSTRACT

It has become increasingly evident from reports in the literature that there are many confounding factors capable of modulating radiation-induced non-targeted responses, such as the bystander effect and the adaptive response. In this paper, we examine recent data which suggest that the observation of non-targeted responses may not be universally observable for differing radiation qualities. We have conducted a study of the adaptive response following low-linear energy transfer exposures for human colon carcinoma cells and failed to observe adaption for the endpoints of clonogenic survival or micronucleus formation.


Subject(s)
Adaptation, Physiological/radiation effects , Bystander Effect/radiation effects , Cell Survival/radiation effects , Colonic Neoplasms/pathology , Colonic Neoplasms/physiopathology , Linear Energy Transfer , Cell Line, Tumor , Dose-Response Relationship, Radiation , Humans , Radiation Dosage
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